Understanding the effect of estrogens on plasma lipoproteins may help to explain the observed lipoprotein differences between males and females, and may help to elucidate the markedly disparate age matched incidence of atherosclerosis between males and females in our population. Premenopausal females have significantly lower VLDL levels and significantly higher HDL2 levels than do males. The higher HDL2 levels can be explained by an estrogen effect. The lower VLDL levels are presumably due to progesterone, the other major ovarian hormone. Further understanding of VLDL and HDL metabolism in normal and dyslipoproteinemic subjects (such as pateints with Tangier disease) may help to elucidate the role of these lipoproteins in free cholesterol and cholesterol ester metabolism. A further definition of the defect in familial type IIa hyperlipoproteinemia will help us to understand regulation of cholesterol plasma levels, and will complement LDL receptor studies which have been carried out in the fibroblasts of these patients.